BNT162b2 vaccine-induced humoral and cellular responses against SARS-CoV-2 variants in Systemic Lupus Erythematosus

ABSTRACT Objectives Our aims were to evaluate Systemic Lupus Erythematosus (SLE) disease activity and SARS-CoV-2 specific immune responses after BNT162b2 vaccination. Methods In this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine, until day 15 after the second dose in 126 SLE patients. SARS-CoV-2 antibody responses were measured against wild-type spike antigen while serum-neutralizing activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T-cell responses were quantified by Interferon (IFN)-γ release assay after the second dose. Results BNT162b2 was well tolerated and no statistically significant variations of BILAG and SLEDAI scores were observed throughout the study in SLE patients with active and inactive disease at baseline. Mycophenolate Mofetil (MMF) and Methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody-response (β=-78; p=0.007, β=-122; p<0.001, respectively). Anti-spike antibody response was positively associated with baseline total IgG serum levels, naïve B cell frequencies (β=2; p=0.018, β=2.5; p=0.003) and SARS-CoV-2-specific T cell response (r=0.462; p=0.003). In responders, serum neutralization activity decreased against VOCs bearing the E484K mutation but remained detectable in a majority of patients. Conclusion MMF, MTX and poor baseline humoral immune status, particularly: low naïve B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating SLE patients who might need adapted vaccine regimens and follow-up. KEY MESSAGES What is already known about this subject? BNT162b2 efficacy and safety has been described in studies mixing different RMDs What does this study add? No serious adverse effects, nor SLE flares have been documented after BNT162b2 in SLE patients. Not only MMF and MTX, but also a poor humoral immune status at baseline impair vaccine antibody response Albeit decreased, serum neutralizing activity against VOCs is conferred to vaccine-responders. How might this impact on clinical practice or future developments? These parameters could be helpful for physicians to delineate which patients should have antibody measurement after full BNT162b2 vaccination and should be proposed a third injection of BNT162b2 vaccine.